Pharmaceutical composition containing 9-ethyl-6, 6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6, 11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

Abstract

The present invention aims to provide a high-dose formulation with improved properties of a pharmaceutical composition comprising a poorly soluble basic agent, particularly a compound represented by formula (I) or a salt thereof. The problem described above can be solved by providing a pharmaceutical composition comprising the compound represented by formula (I) or a salt thereof, a surfactant, and a basic substance.

The invention claimed is: 
     
         1 . A tablet comprising a pharmaceutical composition comprising a compound represented by formula (I) or a salt thereof, a surfactant, a disintegrator, and a basic substance 
       
         
           
           
               
               
           
         
       
       wherein the basic substance is at least one substance selected from the group consisting of magnesium aluminometasilicate, L-arginine, meglumine, magnesium oxide, magnesium hydroxide, and magnesium carbonate,
 wherein the surfactant is sodium lauryl sulfate, and 
 wherein the tablet contains the compound represented by formula (I) or a salt thereof in an amount of 150 mg to 800 mg per unit formulation in terms of the free form and contains the disintegrator in an amount of 5 wt % or more based on the total amount of the pharmaceutical composition. 
 
     
     
         2 . The tablet according to  claim 1 , wherein the disintegrator is at least one substance selected from the group consisting of carmellose calcium, crospovidone, sodium starch glycolate, and croscarmellose sodium. 
     
     
         3 . The tablet according to  claim 1 , wherein the pharmaceutical composition comprises a weight ratio of the compound represented by formula (I) or a salt thereof to the surfactant at a range from 100:3 to 100:50. 
     
     
         4 . The tablet according to  claim 1 , wherein the pharmaceutical composition contains the basic substance in an amount of 5 wt % or more. 
     
     
         5 . The tablet according to  claim 1 , wherein a dissolution rate at 30 minutes is 45% or more as measured by the paddle method for dissolution test specified in the Japanese Pharmacopeia, using the 1st fluid for dissolution test specified in the Japanese Pharmacopeia containing polyoxyethylene (10) octylphenyl ether (4%). 
     
     
         6 . The tablet according to  claim 1 , wherein a dissolution rate at 30 minutes is 60% or more as measured by the paddle method for dissolution test specified in the Japanese Pharmacopeia, using the 1st fluid for dissolution test specified in the Japanese Pharmacopeia containing polyoxyethylene (10) octylphenyl ether (4%). 
     
     
         7 . The tablet according to  claim 1 , wherein a dissolution rate at 30 minutes is 75% or more as measured by the paddle method for dissolution test specified in the Japanese Pharmacopeia, using the 1st fluid for dissolution test specified in the Japanese Pharmacopeia containing polyoxyethylene (10) octylphenyl ether (4%). 
     
     
         8 . The tablet according to  claim 1 , wherein a dissolution rate at 75 minutes is 70% or more as measured by the paddle method for dissolution test specified in the Japanese Pharmacopeia, using the 1st fluid for dissolution test specified in the Japanese Pharmacopeia containing polyoxyethylene (10) octylphenyl ether (4%). 
     
     
         9 . The tablet according to  claim 1 , wherein a dissolution rate at 30 minutes is 45% or more as measured by the paddle method for dissolution test specified in the Japanese Pharmacopeia, using purified water (900 mL) containing formic acid (33 mL) and polyoxyethylene (10) octylphenyl ether (2%). 
     
     
         10 . The tablet according to  claim 1 , wherein a dissolution rate at 30 minutes is 60% or more as measured by the paddle method for dissolution test specified in the Japanese Pharmacopeia, using purified water (900 mL) containing formic acid (33 mL) and polyoxyethylene (10) octylphenyl ether (2%). 
     
     
         11 . The tablet according to  claim 1 , wherein a dissolution rate at 30 minutes is 75% or more as measured by the paddle method for dissolution test specified in the Japanese Pharmacopeia, using purified water (900 mL) containing formic acid (33 mL) and polyoxyethylene (10) octylphenyl ether (2%). 
     
     
         12 . The tablet according to  claim 1 , wherein a dissolution rate at 75 minutes is 70% or more as measured in the paddle method for dissolution test specified in the Japanese Pharmacopeia, using purified water (900 mL) containing formic acid (33 mL) and polyoxyethylene (10) octylphenyl ether (2%). 
     
     
         13 . The tablet according to  claim 1 , wherein a residue of a sample is observed at 30minutes in the disintegration test specified in the Japanese Pharmacopeia using water as a test medium, wherein the residue is a minor amount of a soft substance or a muddy substance. 
     
     
         14 . The tablet according to  claim 1 , wherein no residue of a sample is observed at 30minutes in the disintegration test specified in the Japanese Pharmacopeia using water as a test medium. 
     
     
         15 . The tablet according to  claim 1 , wherein a residue of a sample is observed at 30minutes in the disintegration test specified in the Japanese Pharmacopeia using, as a test medium, the 1st fluid for dissolution test specified in the Japanese Pharmacopeia, wherein the residue is a minor amount of a soft substance or a muddy substance. 
     
     
         16 . The tablet according to  claim 1 , wherein no residue of a sample is observed at 30minutes in the disintegration test specified in the Japanese Pharmacopeia using, as a test medium, the 1st fluid for dissolution test specified in the Japanese Pharmacopeia.